Serum Matrix Gla Protein Research Articles

Comparative Study Evaluating the Effect of the Administration of Vitamin K1 versus Placebo on Vascular Calcification in Haemodialysis Patients

Abstract Background Cardiovascular calcification is a risk factor and contributor to morbidity and mortality in End stage kidney disease patients. Patients with chronic kidney disease develop accelerated calcification of the intima, media, heart valves and myocardium as well as the rare condition of calcific uremic arteriolopathy (calciphylaxis). Pathomechanistically, Cardiovascular calcification is most likely due to an imbalance of promoters (e.g. Calcium and phosphate) and inhibitors (e.g. fetuin-A and matrix Gla protein). Objective to study the effect of oral vitamin k1 on serum Matrix gla protein in patients on maintenance hemodialysis and to study its effect as an important marker of vascular calcification. Patients and Methods This Placebo Controlled clinical trial was conducted for 3 months on 80 adult ESRD patients on regular Hemodialysis recruited from Ain shams university Hospitals hemodialysis unit, their age ranged from 18 to 75 years each participant signed informed consent classified into two groups, with the study group containing 40 patients who received Vitamin K1 therapy 5 mg every other day for three months duration and the control placebo group containing 40 patients who received Placebo every other day for three months duration. Results There was no statistically significant difference between the two groups according to their risk factors regarding smoking, HTN, HCV, DM, and ISHD. In this clinical trial only 29 % of patients were diabetic, but their diabetes was well controlled and there was no significant difference between groups regarding incidence of diabetes. There was no significant difference between groups regarding vascular access (AVF, Double lumen tunneled dialysis catheter) and duration of dialysis (P > 0.05). The current study showed that vitamin k1 therapy resulted in no significant effect in comparison to the placebo group on calcium, phosphorus, calcium-phosphorus product and (P = 0.435), (P = 0.142), (P = 0.191) respectively. Age has non-significant effect on MGP level neither in the study group (P = 0.636) before vitamin k1 therapy nor in the placebo group (P = 0.841) and after vitamin k1 therapy in study group (P = 0.605) and placebo group (P = 0.332). Conclusion Different risk factors including Hypertension, Diabetes Mellitus, Smoking, Heart failure, Ischemic heart disease and hepatitis c virus has no significant effect on serum MGP levels neither before nor after therapy in both study and placebo groups.

Inactive Matrix Gla Protein in Relation to Renal and Cardiac Functions and Cardiac Valvular Calcification Among Type 2 Diabetes Patients.

Matrix Gla protein (MGP) is a robust innate suppressor of the detrimental process of vascular calcification in the human body. The interrelationship between circulating MGP levels and renal and cardiac dysfunction, besides echocardiographic calcification score (ECS) was investigated in a sample of type 2 diabetes (T2D) patients. The study included 130 subjects. They were 95 patients with T2D and 35 age- and sex-matched healthy controls. Patients were further subdivided into 52 T2D patients without DKD (eGFR ⩾ 60 ml/minute/1.73 m²) and 43 T2D persons with DKD (eGFR > 60 ml/minute/1.73 m²). Serum MGP levels, determined by ELISA, renal function tests, lipid profile, and echocardiography were studied in all participants. Significantly elevated circulating inactive MGP level was noted in individuals having T2D compared to controls. It correlated negatively with eGFR and left ventricular (LV) diastolic and systolic functions and positively with indices of LV hypertrophy. ECS was significantly increased in both T2D groups compared to controls and in DKD group compared to the diabetic group without DKD. A significant positive correlation was observed between inactive MGP and ECS. Serum inactive MGP may contribute to the development of DKD and to the associated process of cardiac valvular calcification. It may be a beneficial diagnostic marker for early prediction of cardiac calcification and preclinical LV systolic and diastolic dysfunction in T2D patients, especially in those complicated with DKD.

MO789: The Effect of Oral Vitamin K2 Versus K1 on Vascular Calcification in Hemodialysis Patients: A Randomized Controlled Trial

Abstract BACKGROUND AND AIMS Vascular calcification is a common complication of end-stage renal disease and an important cause of cardiovascular diseases and mortality. Vitamin K is essential for the activation of matrix Gla protein (MGP), a powerful inhibitor of tissue calcification. However, there are limited data on the efficacy and safety of different vitamin K forms on vascular calcification in hemodialysis patients, most of whom are essentially vitamin K deficient. METHOD A prospective, randomized, placebo-controlled clinical trial, that included 120 eligible hemodialysis patients who were randomly assigned to one of three equal study groups: vitamin K1 (10 mg phytomenadione thrice-weekly), vitamin K2 (90 ug daily), or placebo for 3 months. Serum MGP, calcium, phosphorus, their product and intact parathyroid hormone (iPTH) levels were all assessed at baseline and at the end of the study. RESULTS MGP levels showed a significant increase in the vitamin K2 group (700%) compared with (78%) and (40%) in vitamin K1 and placebo groups respectively. No change was found in bone profile at 3 months compared with baseline at both of the treatment groups. No correlations between calcium, phosphorous and PTH and MGP levels at baseline or after treatment. None of the treatment group patients experienced any adverse effects. CONCLUSION Vitamin K supplementation was tolerable and effective in improving levels of a potent calcification inhibitor as MGP, with K2 form showing superiority over K1 in their impact on MGP levels among hemodialysis patients.

Significance of serum glucagon-like peptide-1 and matrix Gla protein levels in patients with diabetes and osteoporosis.

BACKGROUNDOsteoporosis is a systemic bone disease characterized by decreased bone mass, impaired bone mass, and reduced bone strength that leads to increased bone fragility and fracture. Type 2 diabetes mellitus (T2DM) complicated with osteoporosis is a common systemic metabolic bone disease, and reduced bone mass and bone strength are considered the main clinical features; however, the pathogenesis of this disease has not been fully clarified. Its occurrence is considered related to sex, age, and genetic factors. There are many risk factors for diabetes complicated with osteoporosis. Therefore, exploring these risk factors will help prevent it.AIMTo investigate the relationships among serum glucagon-like peptide-1 (GLP-1) levels, matrix Gla protein (MGP) levels, and diabetes with osteoporosis.METHODSSixty patients with T2DM complicated with osteoporosis confirmed by the endocrinology department of our hospital were selected as the case group. Sixty T2DM patients with bone loss were selected as the control group. Sixty healthy participants were selected as the healthy group. The general data, bone mineral density index, and bone metabolic markers of the three groups were compared. The relationships among GLP-1 levels, MGP levels, and the bone mineral density index of the case group were analyzed using linear correlation analysis and a logistic regression model.RESULTSDifferences in sex, smoking, and drinking among the case group, control group, and healthy group were not statistically significant (P > 0.05). The mean age of the case group was older than those of the control and healthy groups (P < 0.05). The body mass index, fasting plasma glucose level, HbA1c level, hypertension rate, and coronary heart disease rate of the case and control groups were higher than those of the healthy group (P < 0.05). The serum GLP-1 and MGP levels of the case group were lower than those of the control and healthy groups; these differences were statistically significant (P < 0.05). The serum GLP-1 and MGP levels of the control group were lower than those of the healthy group; these differences were statistically significant (P < 0.05). The serum GLP-1 and MGP levels of the case group were significantly positively correlated with the bone mineral density values of the hip and lumbar spine (P < 0.05). The results of the logistic regression model showed that age and duration of diabetes were independent risk factors for osteoporosis in diabetic patients (P < 0.05) and that increased GLP-1 and MGP values were protective factors against osteoporosis in diabetic patients (P < 0.05).CONCLUSIONSerum GLP-1 and MGP levels of diabetic patients with osteoporosis were significantly decreased and positively correlated with bone mineral density and were independent risk factors for osteoporosis in diabetic patients.

Predictors of Vascular Calcification in Hemodialysis Patients

Background: The prevalence of both cardiovascular mortality and vascular calcification is much higher in patients with chronic kidney disease (CKD) than in the general population so early detection and intervention of VC may prevent or delay the progression and achieve improved patient outcomes. Objectives: To detect different predictors of vascular calcification in haemodialysis patients. Methods: This was a cross sectional observational study that included 85 patients with end stage renal disease (ESRD) on regular dialysis 47 males and 38 females ranged between 18 and 80 years old selected from Nephrology Unit, Internal Medicine Department, Menoufia University Hospital from April 2019 to May 2020. Serum calcium, phosphorus, alkhaline phosphatase, intact PTH, serum Matrix GLA protein, vitamin D and non-contrast CT for calcium scoring of femoral arteries were performed. Results: There was a significant correlation between age of the patient by years (p value 0.0001), serum calcium (p value 0.0001), phosphate (0.0001), calcium phosphate products (p value 0.0001) and alkhaline phosphatase (0.0001), and vascular calcification score detected by non-contrast CT on femoral arteries and negative correlation between serum Matrix GLA protein p value 0.0001) and the detected calcification score; the lower the MGP level the higher calcification score while there was no correlation between body mass index (BMI) (p value 0.021) intact PTH (p value 0.117), serum vitamin D level (p value 0.643), serum albumin (p value 0.643), serum haemoglobin (p value 0.257) and duration of dialysis (p value 0.260) and the detected score. Serum phosphate and calcium phosphorus product are independent risk factors for vascular calcification severity in haemodialysis patients. Conclusions: serum phosphate, calcium phosphate products are risk factors for vascular calcification while intact PTH vitamin D has no significant role in developing vascular calcification in hemodialysis patients. Matrix GLA protein was inversely correlated with vascular calcification score.

The relationship between calcification inhibitor levels in chronic kidney disease and the development of atherosclerosis

Aim We aimed to investigate the factors affecting the development of atherosclerosis and the role of calcification inhibitors fetuin-A, matrix-Gla protein (MGP), osteoprotegerin (OPG) in atherosclerosis progress. Material and methods The study was planned to investigate the relationship of serum OPG, MGP and fetuin-A levels with the development of atherosclerosis in the stage 2–3–4–5 chronic kidney disease (CKD) patients who did not require dialysis treatment. Results 32 (17 female, 15 male) healthy individuals and 92 (49 females, 43 males) CKD patients were included. The mean carotid intima-media thickness (CIMT), C-reactive protein (CRP), fetuin-A, OPG and MGP of the two groups were compared statistically. In CKD patients, age, body mass index (BMI), CRP, triglyceride, urea, systolic blood pressure (SBP), fasting blood sugar have a positive linear relationship, fetuin-A, OPG, GFR have a negative linear relationship with CIMT. The mean CIMT, right CIMT, left CIMT, blood urea, CRP, urinary albumin excretion creatinine and age show a negative linear relationship with fetuin-A. Conclusion Fetuin-A levels begin to decline from the early stages of CKD and are significantly lower in patients with atherosclerosis as expressed with CIMT. This suggests that fetuin-A may be used as an early marker in CKD for increased cardiovascular risk. Early recognition of these risk factors is important and large-scale studies on vascular calcification inhibitors are needed.

P0195THE RELATIONSHIP BETWEEN CALCIFICATION INHIBITOR LEVELS IN CHRONIC KIDNEY DISEASE AND THE DEVELOPMENT OF ATHEROSCLEROSIS

Abstract Background and Aims Atherosclerosis and its associated cardiovascular diseases starting from the early stages of chronic kidney disease (CKD) are the most important cause of increased morbi-mortality in the CKD process. In studies performed in patients with end-stage renal disease (ESRD), it is observed that the calcification occured in the vascular structures was an important component of the atero-arteriolosclerosis process. The number of studies investigating the relationship between vascular calcification and the development of atherosclerosis and increased morbi-mortality in the process of CKD are quite small and limited to patients undergoing hemodialysis (HD) treatment for ESRD. We aimed to investigate the factors affecting the development of atherosclerosis and the role of calcification inhibitors fetuin-A, matrix-Gla protein (MGP), osteoprotegerin (OPG) in atherosclerosis progress. Method Our study was planned to investigate the relationship of serum OPG, MGP and fetuin-A levels with the development of atherosclerosis in the stage 2-3-4-5 chronic kidney patients who did not require dialysis treatment. Thirty-two (17 female, 15 male) healthy individuals and 92 (49 females, 43 males) CKD cases were included. The healthy control group did not have a history of regular use of medication for any reason, known acute or chronic disease. Chronic kidney disease group, with no acute disease, no history of known malignancy and cerebrovascular disease. The patients' GFR was also calculated with CKD-EPI Formula. The mean carotid artery intima media thickness was calculated by dividing the sum of right and left carotid artery intima media thickness. Statistical analysis was performed with IBM SPSS Statistics 20.0.0. Results The laboratory data of the healthy control group, stage 2 CKD group, stage 3 CKD group, stage 4 CKD group and stage 5 CKD groups were statistically compared with the healthy control group, between themselves and the whole CKD group, the results were given in Table-1. Chronic kidney disease group divided into two groups; carotid artery intima media thickness less than 0.750 millimeters (without subclinical atherosclerosis) and those above 0.750 millimeters (with subclinical atherosclerosis). The mean C-IMT, CRP, FETUIN-A, OPG and MGP of the two groups were compared statistically and the results are shown in Table-2. In chronic kidney patients, age (r = 0.493, p &amp;lt;0.001), BMI (r = 0.337, p = 0.001), CRP (r = 0.301, p = 0.004), TG (r = 0.245, p = 0.019 ), urea (r = 0.228, p = 0.029), SBP (r = 0.212, p = 0.043), fasting blood sugar (r = 0.212, p = 0.043) have positive linear relationship, fetuin-A (r = -0.409, P = 0.001), OPG (r = -0.235, p = 0.024), GFR (r = -0.209, p = 0.046) have a negative linear relationship with CIMT. The multiple relationships between CIMT and other variables are given in Table-3. The mean CIMT (r =-0.417, p = 0.001), right CIMT (r = -0.412, p = 0.001), left CIMT (r = -0.410, p = 0.001), urea (r = -353, p = 0.007), CRP (r = -0.322, p = 0.014), UPE (r = -0.301, p = 0.022), creatinine (r = -0.277, p = 0.035), age (r = -0.262, p = 0.047) show a negative linear relationship with Fetuin-A. Multiple relationships between fetuin-A and other variables are given in Table-4. Conclusion Our study shows that; In particular, fetuin-A levels, which is a vascular calcification inhibitor, begin to decline from the early stages of CKD and is significantly lower in patients with atherosclerosis. This suggests that fetuin-A may be used as an early marker in CKD with increased cardiovascular mortality. On the other hand, contradictions related to the levels of OPG and MGP in CKD and its role in the development of atherosclerosis continue. The results in our study also support this situation. Reducing mortality and morbidity in CKD primarily depends on reducing the risk of cardiovascular events. Pre-recognition of these risks is important, so large-scale studies on vascular calcification inhibitors are needed.

Association of Genetic Polymorphisms in the Matrix Gla Protein (MGP) Gene with Coronary Artery Disease and Serum MGP Levels.

Matrix Gla protein (MGP) is an important regulatory protein for inhibition of calcification in the vessel wall and cartilage. The MGP gene polymorphisms are suspected to increase the risk of extracellular calcification through altering the related gene expression and serum MGP levels. The goal of this study was to examine the correlation between rs4236 (Thr83-Ala), rs12304 (Glu60-X) and rs1800802 (T138-C) polymorphisms of the MGP gene and coronary artery calcification. Serum MGP levels of 168 subjects who had undergone coronary angiography were analyzed along with genotyping of MGP gene polymorphisms. The results indicated that serum MGP levels were significantly associated with rs4236 and rs1800802 polymorphisms of the MGP gene with the occurrence of coronary artery diseases (CAD). Allelic distributions of MGP gene polymorphisms and serum MGP levels, respectively, were not significantly interconnected with the presence of CAD. Our results revealed that serum MGP levels of CAD patients show association with rs4236 and rs1800802 polymorphisms, but serum MGP levels alone do not directly reflect the risk of CAD. The role of MGP genetic variants on formation and progression of arterial calcification should be regarded in cardiovascular diseases.

623: Decreased myometrial expression of matrix-Gla protein (MGP) is associated with preterm and term laboring state

Uterine contractions are driven by complex calcium mediated mechanisms. Matrix Gla-protein (MGP) is an emerging vitamin K2-dependent protein with key roles in calcium homeostasis and inhibition of smooth muscle calcification. We sought to study MGP expression to provide new insight into the physiology of term and preterm contracting human myometrium. Myometrial expression of MGP was investigated in the following groups: 1) term labor (TL, n=5, GA: 39); 2) term non-labor (TNL, n=5, GA: 39); 3) preterm labor (PTL, n=5, GA: 28); 4) preterm non-labor (PTNL, n=13, GA: 29). Serum levels of MGP were measured by ELISA. Myometrial expression was assessed using immunohistochemistry and RNAseq with qRT-PCR validation. MGP and calcium-related proteins were localized with immunofluorescence in pregnant (PHM1) and non-pregnant (hTERT) human myometrial cell lines. 1) Pregnant myometrial cell lines had greater expression of MGP compared to non-pregnant state (Figure A). 2) At term, maternal serum MGP levels were unaffected by labor. 3) Cytoplasm of human myocytes display MGP immunostaining constitutively. 4) By qRT-PCR, we identified significantly higher levels of MGP gene expression in non-laboring myometrium compared to laboring preterm (p=0.002) and term (p=0.0004) tissues (Figure B). 5) This expression pattern was paralleled in mRNAseq of term (p=0.003) and preterm (p=0.002) uterus. 6) Immunocytochemistry showed that MGP colocalized with smooth-muscle actin monofilaments, but not calcium exchangers (SERCA, PMCA1) and Golgi marker. Our study presents the novel findings that MGP is present in human myometrium, and its tissue withdrawal is associated with a laboring state.

Association of matrix γ-carboxyglutamic acid protein levels with insulin resistance and Lp(a) in diabetes: A cross-sectional study.

The risk of cardiovascular disease (CVD) and mortality is increased in patients with chronic kidney disease (CKD), with a background role of vascular calcification in the development of CVD also reported. Studies have demonstrated that high lipoprotein(a) (Lp(a)) levels accelerate the development of atherosclerolsis and are potentially involved in the vascular calcification. Matrix Gla Protein (MGP) seems to play an important role in vascular calcification. The aim of the study was to examine the potential association of MGP concentrations with Lp(a) and insulin resistance. The study involved 100patients divided in four groups: 25 with both CKD stage 4 and Type2 Diabetes (DM) (Group-A), 25 with CKD4 without DM (Group-B), 25 non uremic patients with DM (Group-C) and 25 healthy subjects (Group-D). Serum glucose, Lp(a), MGP, plasma HBA1c and insulin were measured in all patients. Insulin resistance was estimated by the homeostasis model assessment equation (HOMA-IR). A significant positive linear association between MGP and Lp(a) levels (r=0.272, p=0.006) was noted, as well as between MGP and HOMA-IR levels (r=0.308, p=0.002). However, no significant linear association between Lp(a) and HOMA-IR levels was recorded. A similar positive association between MGP and insulin levels (r=0.204, p=0.042) was also found. This study concluded that diabetes coexisting with renal disease leads to extreme vascular calcification expressed by elevated MGP levels, resulting in higher frequency of cardiovascular disease in comparison to CKD patients without diabetes. The detected Lp(a) and MGP association in CKD4 patients may also represent the key to the complicated mechanism of their coexisting accelerated atherosclerosis and vascular calcification.

Enhanced serum levels of matrix Gla protein and bone morphogenetic protein in acute coronary syndrome patients.

Vascular calcification has been found to be associated with increased risk of cardiovascular (CV) morbidity and mortality. Various bone-associated proteins have been suggested to be related with this process. In this study, we aimed to evaluate whether serum levels of bone morphogenic protein-4 (BMP-4) and matrix Gla protein (MGP) differed in patients who were found to have normal epicardial coronary arteries or a culprit lesion in the coronary angiography leading to acute coronary syndrome (ACS). Patients admitted to emergency department with the diagnosis of ACS who underwent primary percutaneous coronary intervention (PCI) between October 2015 and April 2016 were consecutively recruited as the patient group. Age and gender-matched subjects who underwent coronary angiography following non-invasive ischemia assessment made the control group. A total of 90 subjects (63.00±14.02years, 70% male) were included in this study. MGP (<0.001) and BMP-4 (<0.001) levels were significantly elevated when compared to subjects with normal coronary arteries. Fasting blood glucose (P=.024), HDL-cholesterol (P=.002), C-reactive protein (CRP) (P=.001) levels, and left ventricular ejection fraction (LVEF) (P=.021) were significantly correlated with serum MGP levels. HDL-cholesterol (P=.001) and CRP (P=.030) levels were also significantly correlated with serum BMP-4 levels. In the model including HDL-cholesterol, CRP, MGP, and BMP-4 levels, only MGP (odds ratio[OR]: 1.018, P=.019) and BMP-4 (OR: 1.313, P=.023) were found to be independently associated with ACS. This study shows that serum BMP-4 and MGP are independently associated with ACS occurrence when adjusted for other CV risk factors. These biomarkers may have a diagnostic potential in ACS patients.

Systemic inflammatory response and calcification markers in patients with long lasting moderate-severe chronic spontaneous urticaria.

Low grade inflammation is associated with both chronic spontaneous urticaria (CSU) and atherosclerosis. Data regarding an association between urticarial inflammation and atherosclerosis and subsequent cardiovascular events are scarce. It has been demonstrated that matrix GLA protein (MGP), a biomarker of arterial calcification, is increased in patients with atherosclerosis. To evaluate circulating levels of markers of arterial calcification and acute phase response (APR) in patients with CSU. Concentrations of MGP and IL-6 were measured in venous blood samples of patients with long-lasting moderate-severe CSU. There were no significant differences in serum MGP concentration between healthy subjects and CU patients. Serum IL-6 concentration was significantly higher in CSU patients as compared with healthy subjects. The results confirm that CSU is accompanied by a low grade systemic inflammatory state. However, the long lasting urticarial inflammation was not paralleled by an increased circulating level of the calcification marker matrix Gla protein.

Osteoprotegerin (OPG) and Matrix Gla protein (MGP) in rheumatoid arthritis patients: Relation to disease activity

BackgroundImbalanced Matrix Gla protein (MGP) and Osteoprotegerin (OPG) levels occur in inflammatory diseases. Aim of the workThe aim of the present study was to evaluate serum MGP and OPG levels in Rheumatoid Arthritis (RA) patients and study their relation to the disease activity. Patients and methodsForty-five female RA patients and 45 age and sex-matched healthy controls were included in this study. Disease activity score 28-C-reactive protein (DAS28-CRP) was used for the assessment of disease activity. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), MGP and OPG were measured in patients and controls. The associations of MGP and OPG with DAS28-CRP and the other laboratory and clinical variables were analyzed. ResultsRA patients had significantly higher serum OPG levels (408.3±520.9pg/ml) and hs-CRP (2.8±1.9mg/l) than the control (92.5±86.3pg/ml and 0.9±1.5mg/l respectively) (p<0.001 each). There was no significant difference in MGP levels between the patients and control (p=0.3). The correlation of OPG and MGP with DAS28-CRP in the patients was insignificant (p=0.4 and p=0.8 respectively). Age positively correlated with OPG (r=0.32, p=0.02), but not with MGP concentration (r=0.05, p=0.64) in the RA patients. ConclusionsThe significant elevation of the OPG level in RA patients may through light on its possible role in the pathogenesis of this disease and could be considered as a future therapeutic target. The significant correlation with age suggests that OPG may be an important mediator especially in elderly RA cases.

Matrix Gla protein (MGP) promoter polymorphic variants and its serum level in stenosis of coronary artery

Although the role of matrix Gla protein (MGP) is not completely known but, its expression within subendothelial macrophages and vascular smooth muscle cells is suggested to be involved in vascular calcification. In this study, we investigated the associations between the serum MGP levels and the MGP promoter high minor allele frequency (MAF) variants with the development of stenosis in coronary arteries. Moreover, we evaluated the allele changes within predicted transcription factor elements with bioinformatics tools. 182 subjects were recruited from who underwent coronary angiography. The MGP promoter rs1800801, rs1800802 and rs1800799 genotypes and haplotypes were detected by ARMS-RFLP PCR techniques. The serum MGP concentration was measured using ELISA method. Jaspar profiles were used for scoring the polymorphic variations within the transcription factor elements. The genotype and two-allelic haplotype distributions were not significant between the patient and control groups (P>0.05). The serum MGP levels had not significant differences between the genotypes (P>0.1) and haplotypes (P>0.4). Based on the prediction studies, we did not observe significant differences between the polymorphic scores in the predicted elements (P>0.05). We concluded that the genotype and haplotype distributions of the MGP promoter high-MAF polymorphisms, as confirmed in the prediction studies and the serum MGP level are not significantly associated with the coronary artery disease. Based on the study results, the MGP protein did not play an important role in the development of stenosis of coronary arteries.

Effect of serum FGF‐23, MGP and fetuin‐A on calcium‐phosphate metabolism in maintenance hemodialysis patients

This study was aimed to explore the role of serum fibroblast growth factor (FGF)-23, matrix Gla protein (MGP) and fetuin-A in the calcium-phosphate metabolism and their predicting value in coronary artery calcification in maintenance hemodialysis (MHD) patients. This study included 64 patients who receive hemodialysis in our hospital. The serum FGF-23, MGP and fetuin-A were analyzed by enzyme-linked immunosorbent assay (ELlSA). Coronary artery calcification score (CACS) was evaluated by coronary artery computed tomography scan. The 64 patients (30 males, 34 females, 60.6 ± 11.3 years of age) received an average dialysis vintage of 6.88 ± 2.94 years. We divided the CACS into three levels, and 13 (20.31%), 16 (25%), and 35 (54.69%) exhibited a CACS of 0-100, 100-400, and >400, respectively. Dialysis vintage, serum FGF-23, fetuin-A, phosphorus and high-density lipoprotein-C levels were identified as independent variables of CACS by stepwise multiple regression analysis. The area under receiver operating characteristic curve indicated that serum FGF-23 and fetuin-A were useful for identifying CAC in MHD patients. The cut-off value corresponding to the highest Youden's index was serum FGF-23 ≥ 256 pg/mL and fetuin-A ≤ 85 μg/mL, which was defined as the optimal predictors of CAC. Different combinations of serum FGF-23 and fetuin-A in parallel or in series effectively boosted the identification of CAC. The incidence of CAC is high in MHD patients. Serum FGF-23 and fetuin-A levels are closely correlated with CAC.

Circulating matrix Gla protein: a potential tool to identify minor carotid stenosis with calcification in a risk population

Carotid calcification is an independent marker for future ischemic events, which are more frequently encountered in postmenopausal women as the prevalence of type 2 diabetes mellitus (T2DM) and hypertension (HT) increases. Matrix Gla protein (MGP) is a major inhibitor of vascular calcification. Here, we report on the prospect of serum MGP to become an identifying tool for minor carotid stenosis (minCAS) with calcification in a risk population. Based on carotid ultrasound examination, out of 72 enrolled postmenopausal women, 33 had minCAS with carotid calcification (minCAS group) and 39 were without minCAS and carotid calcification (non-minCAS group). Serum total MGP, high-sensitivity C-reactive protein (hs-CRP), bone mineral density (BMD) and carotid intima-media thickness (CIMT) were determined. We found significantly elevated serum MGP levels in the minCAS compared to the non-minCAS group (p < 0.05). MGP was independently associated with hs-CRP (unstandardized β -regression coefficient = 2.6; 95 % CI 0.007 – 5.3; p = 0.049) and CIMT ( β = – 611.3; 95 % CI – 1172.6 – – 49.9; p = 0.034) within the minCAS group, but not with BMD. Furthermore, significantly higher MGP levels were determined in two minCAS subgroups (one with HT or T2DM and second with both diseases) compared to a non-minCAS subgroup with HT or T2DM (p < 0.05 and p < 0.01, respectively). A threshold of 87.9 μ g/L serum MGP (area under the receiver operating characteristic = 0.72 } 0.06; 95 % CI 0.60 – 0.84; p = 0.001) may identify minCAS with calcification in postmenopausal women with 63 % precision. Higher circulating MGP levels could help identify minCAS with calcification in a relatively homogenous risk population (i.e., postmenopausal women), regardless of underlying cardiovascular risk factors.

The effect of parathyroid hormone on expression of matrix GLA protein in ovariectomized SD rats and primary osteoblasts

Objective To observe the effect of parathyroid hormone on expression of matrix GLA protein (MGP) in ovariectomized SD rats and primary osteoblast,and to study the role of MGP on the possible mechanism of postmenopausal osteoporosis.Methods Thirty-six Sprague-Dawley female rats were allocated into 3 groups,12 in each:sham operation group,ovariectomized group( OVX group),ovariectomized and parathyroid hormone treatment group.Animals in the parathyroid hormone group were injected parathyroid hormone (20 μg/kg,three times a week for 12 weeks) three weeks after ovariectomy.All rats were sacrificed after 18 weeks.Urine and serum were collected every three weeks.Lumbar vertebral bones were observed by immunohistochemistry.Bone mineral density (BMD) of lumbar vertebra of rats was determined.The content of MGP in serum and urine was determined by enzyme-linked immunosorbent assay (ELISA).Expression of undercarboxylated Matrix GLA Protein (ucMGP) was detected by immunochistochemistry.Relative quantification of MGP mRNA expression in lumbar vertebra bone was detected by Fluorescent real-time quantitative polymerause chain reaction.Results ( 1 ) 18 weeks after ovariectomy,BMD of lumbar vertebra in OVX group was lower than those in sham group and parathyroid hormone group significantly ( P＜0.05 ).(2) The content of MGP in serum and urine was dynamic variation after treatment hy parathyroid hormone,and it was significant compared with OVX group ( P＜0.05 ).( 3 ) Immunohistochemical localization of ucMGP was seen in lumbar vertebra in OVX group.(4) Relative quantification of MGP mRNA expression in lumbar vertebra in OVX group was increased significantly compared with other groups ( P＜0.01 ).( 5 ) parathyroid hormone ( 1-34 ) in 10-7mol/L,10-8mol/L,10-9 mol/L up-regulated MGP mRNA expression in primary osteoblasts about 6.78,5.31,and 2.23 times than control respectively.It was in a dose-dependent manner.Conclusion The effect of parathyroid hormone on the expression of matrix gla protein may play an important role in mechanism of postmenopausal osteoporosis Key words: Parathyroid hormone; Ovariectomized rats; Matrix GLA protein; Postmenopausal osteoporosis

Serum Levels of Calcification Inhibitors in Patients With Intracerebral Hemorrhage

ABSTRACTThe vascular calcification regulators and inflammatory markers including fetuin-A, osteopontin (OPN), and matrix Gla protein (MGP) may play an important role in the development of intracerebral hemorrhages (ICHs). So far, the relationship between these parameters and ICH has not been studied. Therefore, this study was designed to elucidate whether fetuin-A, MGP, and OPN are involved in the pathophysiology of ICH. The ICH group consisted of 27 consecutive patients with spontaneous ICH evaluated in the neurology intensive care unit within the first 24 hours from the onset of the stroke. The serum OPN levels were significantly increased in patients with ICH compared to the controls. On the other hand, the serum MGP and fetuin-A levels were significantly decreased in the patients with ICH in comparison to the controls. In the patients with ICH, the serum MGP levels of the nonsurvivors were statistically significantly lower than the MGP levels of the survivors. In conclusion, the change in serum fetuin-A, MGP, and OPN levels after ICH indicates that these parameters play a role in the pathophysiological processes leading to an ICH. Measurement of the serum MGP levels may also be of value to estimate mortality.

Evaluation of serum matrix Gla protein with osteoprotegerin in patients with rheumatoid arthritis

Evaluation of serum matrix Gla protein with osteoprotegerin in patients with rheumatoid arthritis

Assessment of Matrix Gla Protein, Klotho Gene Polymorphisms, and Oxidative Stress in Chronic Kidney Disease

Increased vascular calcification and oxidative stress are considered as extra renal risk factors at the pathogenesis cardiovascular events in chronic kidney disease (CKD). We investigated matrix Gla protein (MGP) (T-138C, Glu60X, Thr83Ala) and Klotho (Cys370Ser) gene polymorphisms, serum MGP levels, and oxidative stress status of 84 CKD patients and 37 healthy controls. The MGP gene Glu60X and Thr83Ala polymorphisms were significantly associated with CKD. The correlation between T-138C genotype of MGP gene, Cys370Ser genotype of Klotho gene, and CKD was not significant (p > 0.05). At the haplotype analysis, the combination of the X allele of Glu60X and the Thr allele of Thr83Ala showed a significantly increased risk of CKD (p < 0.05). X allele, Thr allele, and C allele of T-138C were associated with diabetes mellitus and CKD phenotypes occurring concurrently (p < 0.01). Serum zinc levels were significantly low in end-stage renal disease (ESRD) patients (p = 0.0001). The total comet score frequency of ESRD patients was higher than that of control group (p < 0.05). The urinary 8-hydroxy-2′-deoxyguanosine levels were significantly high in CKD patients (p < 0.05). According to this study, analyzing the distribution of MGP gene and oxidative stress status would be very informative in order to detect their role at CKD.